A Study to Evaluate the Efficacy and Safety of ASP1707 in Postmenopausal Female Patients With Rheumatoid Arthritis Taking Methotrexate

Phase IIa Study of ASP1707 A Randomized, Placebo-Controlled, Double-Blind, Parallel Group Phase 2a Study of ASP1707 in Postmenopausal Female Patients With Rheumatoid Arthritis (RA) Taking Methotrexate (MTX)

The objective of this study is to evaluate the efficacy, pharmacokinetics, pharmacodynamics and safety of ASP1707 in combination with MTX in postmenopausal female patients with RA.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Placebo; Drug: ASP1707; Drug: Methotrexate

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
    • Site JP00022
  • Aichi, Japan
    • Site JP00023
  • Chiba, Japan
    • Site JP00017
  • Ehime, Japan
    • Site JP00026
  • Fukui, Japan
    • Site JP00025
  • Fukuoka, Japan
    • Site JP00012
  • Fukuoka, Japan
    • Site JP00018
  • Fukuoka, Japan
    • Site JP00019
  • Gunma, Japan
    • Site JP00006
  • Gunma, Japan
    • Site JP00024
  • Hiroshima, Japan
    • Site JP00010
  • Hiroshima, Japan
    • Site JP00011
  • Hokkaido, Japan
    • Site JP00001
  • Hokkaido, Japan
    • Site JP00002
  • Hokkaido, Japan
    • Site JP00003
  • Iwate, Japan
    • Site JP00004
  • Iwate, Japan
    • Site JP00005
  • Kagoshima, Japan
    • Site JP00016
  • Kanagawa, Japan
    • Site JP00021
  • Kanagawa, Japan
    • Site JP00007
  • Kumamoto, Japan
    • Site JP00014
  • Kumamoto, Japan
    • Site JP00015
  • Nagasaki, Japan
    • Site JP00013
  • Oita, Japan
    • Site JP00020
  • Shizuoka, Japan
    • Site JP00008
  • Shizuoka, Japan
    • Site JP00009
  • Tokyo, Japan
    • Site JP00027

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject has RA that was diagnosed according to the 1987 ACR criteria or the 2010 ACR/EULAR criteria.
• Subject meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class I, II or, III.

• subject has active RA as evidenced by both of the followings:

  • ≥ 6 tender/painful joints (using 68-joint assessment)
  • ≥ 6 swollen joints (using 66-joint assessment)
• CRP (C-reactive protein) of > 0.3 mg/dL or ESR (Erythrocyte sedimentation rate) of > 28 mm/hr at screening.
• Subject who continuously received MTX and who is able to continue stable dose of MTX.
• Subject who did not receive the following drugs, or received the drugs with stable dosage:

Non-steroidal anti-inflammatory drugs, oral morphine or equivalent opioid analgesics, acetaminophen, or oral corticosteroids.

Exclusion Criteria:

• Inadequate responders to a biologic DMARD (Disease-modifying antirheumatic drug).
• Subject has taken other investigational research products are prohibited within 12 weeks (84 days) or within 5 half-lives, whichever is longer, prior to screening.
• Subject has undergone surgery which has residual effects on the assessed joints, or is scheduled to undergo surgery that may affect the study evaluation of the assessed joints.
• Subject has another type of inflammatory arthritis other than RA.

• Subject who meets any of the following criteria of laboratory values at screening:

  • White blood cell count <4000/μL
  • Platelet count <100000/μL
  • ALT (Alanine Aminotransferase) ≥ 2 x ULN (Upper Limit of Normal)
  • AST (Aspartate Aminotransferase) ≥ 2 x ULN
  • Total bilirubin ≥ 1.5 x ULN
  • Positive Hepatitis B surface antigen, Hepatitis B virus-DNA quantitation, or Hepatitis C virus antibody
• Subject has a positive QuantiFERON-TB Gold test or T-spot.
• Subject has a history of or concurrent malignant tumor.
• Subject has any ongoing severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, infectious, or autoimmune disease except for RA, or diseases which preclude the subject's participation in the study.
• Subject has a history of clinically significant allergy.
• Subject has clinically significant abnormalities on the 12-lead Electrocardiogram.
• Subject has a history of positive Human Immunodeficiency Virus infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASP1707; ASP1707 will be orally administered for 12 weeks.	Drug: ASP1707; Oral; Drug: Methotrexate; Methotrexate will be orally administered at stable dose from at least 28 days prior to screening through the screening and treatment periods until the end of the follow-up period.
Placebo Comparator: Placebo; Placebo will be orally administered for 12 weeks.	Drug: Placebo; Oral; Drug: Methotrexate; Methotrexate will be orally administered at stable dose from at least 28 days prior to screening through the screening and treatment periods until the end of the follow-up period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR20 response rate	ACR20: American College of Rheumatology 20	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR20 response rate		Up to Week 8
ACR50 response rate		Up to Week 12
ACR70 response rate		Up to Week 12
Change from baseline in DAS28-CRP score	DAS28-CRP: Disease Activity Score28 - C-reactive protein	Baseline and Up to Week 12
Change from baseline in DAS28-ESR score	DAS28-ESR: Disease Activity Score28 - Erythrocyte sedimentation rate	Baseline and Up to Week 12
Change from baseline in Tender Joint Count (68 joints)		Baseline and Up to Week 12
Change from baseline in Swollen Joint Count (66 joints)		Baseline and Up to Week 12
Percentage of subjects achieving DAS28-CRP score and DAS28-ESR score for remission (<2.6)		Up to Week 12
Percentage of subjects achieving DAS28-CRP score and DAS28-ESR score for low disease activity (≤3.2)		Up to Week 12
Change from baseline in CRP		Baseline and Up to Week 12
Change from baseline in ESR		Baseline and Up to Week 12
Percentage of subjects achieving EULAR response criterion of "Good Response"	EULAR: European league Against Rheumatism	Up to Week 12
Percentage of subjects achieving EULAR response criterion of "Good Response" or "Moderate Response"		Up to Week 12
Percentage of subjects achieving ACR/EULAR score for remission		Up to Week 12
Percentage of subjects achieving SDAI score ≦ 3.3 (SDAI remission)	SDAI: Simplified Disease Activity Index	Up to Week 12
Change from baseline in the SDAI score		Baseline and Up to Week 12
Change from baseline for the HAQ-DI	HAQ-DI: Health Assessment Questionnaire - Disability Index	Baseline and Up to Week 12
Safety assessed by incidence of adverse events		Up to Week 13
Safety assessed by body temperature		Up to Week 13
Safety assessed by pulse rate		Up to Week 13
Safety assessed by blood pressure in sitting position		Up to Week 13
Safety assessed by laboratory tests: Hematology		Up to Week 13
Safety assessed by laboratory tests: Biochemistry		Up to Week 13
Safety assessed by laboratory tests: Urinalysis		Up to Week 13
Safety assessed by standard 12-lead electrocardiogram		Up to Week 13
Safety assessed by weight		Up to Week 13
Plasma concentration of ASP1707		Up to Week 12
Plasma concentration of metabolite of ASP1707		Up to Week 12
Pharmacodynamics assessed by endocrinology tests		Up to Week 13
Pharmacodynamics assessed by plasma concentration of TNF-α	TNF: Tumor Necrosis Factor	Up to Week 13
Pharmacodynamics assessed by plasma concentration of MMP3	MMP3: Matrix metalloproteinase 3	Up to Week 13
Pharmacodynamics assessed by plasma concentration of IL-6	IL-6: Interleukin-6	Up to Week 13

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Medical Director, Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2016
• Primary Completion (Actual): October 18, 2017
• Study Completion (Actual): October 25, 2017

Study Registration Dates

• First Submitted: August 26, 2016
• First Submitted That Met QC Criteria: August 26, 2016
• First Posted (Estimated): August 31, 2016

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Methotrexate; Rheumatoid arthritis; ASP1707
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Rheumatoid; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites; Dermatologic Agents; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Methotrexate
• Other Study ID Numbers: 1707-CL-3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR